scholarly journals Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Daniela Hoeber ◽  
Marco Sifringer ◽  
Yohan van de Looij ◽  
Josephine Herz ◽  
Stéphane V. Sizonenko ◽  
...  
Keyword(s):  
Brain Injury ◽  
White Matter ◽  
Neuronal Plasticity ◽  
Memory Function ◽  
Neurodevelopmental Outcome ◽  
Cognitive Outcome ◽  
Neonatal Brain ◽  
Adult Rats ◽  
Adult Age

Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80% oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

P.4.003 White matter alterations following traumatic brain injury in mice may account for long term fear extinction deficits

2016 ◽  
Vol 26 ◽  
pp. S87-S88
Author(s):  
M. Ouradou ◽  
Y. Zhu ◽  
E. Deou ◽  
C. Leconte ◽  
V. Besson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Fear Extinction

scholarly journals Long-term neurodevelopment in children born with esophageal atresia: a systematic review

2021 ◽  
Author(s):  
Camille E van Hoorn ◽  
Chantal A ten Kate ◽  
Andre B Rietman ◽  
Leontien C C Toussaint-Duyster ◽  
Robert Jan Stolker ◽  
...  
Keyword(s):  
Cognitive Development ◽  
Motor Function ◽  
Esophageal Atresia ◽  
Current Knowledge ◽  
Neurodevelopmental Outcome ◽  
Cognitive Outcome ◽  
Term Outcome ◽  
Long Term Outcome ◽  
The One

Summary Background Although the survival rate of esophageal atresia (EA) has increased to over 90%, the risk of functional long-term neurodevelopmental deficits is uncertain. Studies on long-term outcomes of children with EA show conflicting results. Therefore, we provide an overview of the current knowledge on the long-term neurodevelopmental outcome of children with EA. Methods We performed a structured literature search in Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google scholar on November 8, 2020 with the keywords ‘esophageal atresia’, ‘long-term outcome’, ‘motor development’, ‘cognitive development’, and ‘neurodevelopment’. Results The initial search identified 945 studies, of which 15 were included. Five of these published outcomes of multiple tests or tested at multiple ages. Regarding infants, one of six studies found impaired neurodevelopment at 1 year of age. Regarding preschoolers, two of five studies found impaired neurodevelopment; the one study assessing cognitive development found normal cognitive outcome. Both studies on motor function reported impairment. Regarding school-agers, the one study on neurodevelopmental outcome reported impairment. Cognitive impairment was found in two out of four studies, and motor function was impaired in both studies studying motor function. Conclusions Long-term neurodevelopment of children born with EA has been assessed with various instruments, with contrasting results. Impairments were mostly found in motor function, but also in cognitive performance. Generally, the long-term outcome of these children is reason for concern. Structured, multidisciplinary long-term follow-up programs for children born with EA would allow to timely detect neurodevelopmental impairments and to intervene, if necessary.

306 GCS Does Not Predict Cognitive Outcome 30 Years After Severe Traumatic Brain Injury

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 264-265
Author(s):  
Molly E Hubbard ◽  
Abdullah Bin Zahid ◽  
Gabrielle Meyer ◽  
Kathleen Vonderhaar ◽  
David Y Balser ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Assessment Tool ◽  
Cognitive Status ◽  
Cognitive Outcomes ◽  
Cognitive Outcome ◽  
Symptom Severity Score ◽  
History Of ◽  
Severe Tbi

Abstract INTRODUCTION Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the US. The effects of TBI on quality of life may not become apparent for years after the injury. There are conflicting reports in the literature regarding long term outcomes. Physicians are often asked to predict long term functional and cognitive outcomes, with limited data available. METHODS Patients with severe TBI (GCS = 9) who previously participated in a clinical trial during the 1980s were followed up with and compared to healthy controls without history of TBI. A health questionnaire, sports concussion assessment tool version 3 (SCAT3) and the Telephone Interview for Cognitive Status-modified (TICS-m) were completed over the phone and compared with controls using t-test. GCS at admission and 12-month GRS were used to predict to TICS-M at 30 years using linear regression. RESULTS >45 of the initial 168 subjects were confirmed alive, and 37 (13 females; mean age: 52.43 years S.D. 10.7) consented. Controls (n = 58; 23 females; mean age = 54 years, S.D. 11.5) had lower symptom severity score (6.7 S.D. 12.6 versus 20.6 S.D. 25.3; P = 0.005), lower total number of symptoms (3.4 S.D. 4.7 versus 7.12 S.D. 6.5; P = 0.006), higher standardized assessment of concussion score (25.6 S.D. 2.8 versus 21.2 S.D. 6.9; P = 0.001), and lower corrected MPAI-4 (22.3 S.D. 17.0 versus 43.7 S.D. 12.8; P < 0.001). GCS at admission did not predict cognitive status at 30-years assessed using TICS-M (P = 0.345). The Glasgow Outcome Scale score at 12-months was correlated to TICS-M at 30 years (R = 0.548, P < 0.001); each point decrease in GOS decreasing the score at TICS-M by 5.6 points. CONCLUSION Remote history of TBI disrupts the lives of survivors long after injury. Admission GCS does not predict cognitive status 30 years after TBI. The GOS at 12-months predicted the cognitive status assessed using TICS-M score at 30 years.

scholarly journals PET-detectable tau pathology correlates with long-term neuropsychiatric outcomes in patients with traumatic brain injury

Brain ◽  
2019 ◽  
Vol 142 (10) ◽  
pp. 3265-3279 ◽  
Author(s):  
Keisuke Takahata ◽  
Yasuyuki Kimura ◽  
Naruhiko Sahara ◽  
Shunsuke Koga ◽  
Hitoshi Shimada ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Late Onset ◽  
Neuropsychiatric Symptoms ◽  
Tau Pathology ◽  
Long Term Outcomes

Is tau load associated with long-term outcomes of TBI? By using PET to assess tau deposits in patients with chronic TBI, Takahata et al. reveal elevated tau load compared to age-matched controls, and show that the abundance of tau in white matter is associated with late-onset neuropsychiatric symptoms.

scholarly journals Long-Term White Matter Changes after Severe Traumatic Brain Injury: A 5-Year Prospective Cohort

2013 ◽  
Vol 35 (1) ◽  
pp. 23-29 ◽  
Author(s):  
J. Dinkel ◽  
A. Drier ◽  
O. Khalilzadeh ◽  
V. Perlbarg ◽  
V. Czernecki ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Severe Traumatic Brain Injury ◽  
Prospective Cohort ◽  
White Matter Changes

Biomarkers of brain injury and neurologic outcomes in children treated with chemotherapy for acute lymphoblastic leukemia (ALL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10521-10521
Author(s):  
Yin Ting Cheung ◽  
Raja B. Khan ◽  
Wei Liu ◽  
Tara M. Brinkman ◽  
Michelle N. Edelmann ◽  
...  
Keyword(s):  
Brain Injury ◽  
White Matter ◽  
Linear Models ◽  
Diffusion Tensor ◽  
Neuronal Damage ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Chemotherapy ◽  
Csf Biomarkers ◽  
T Tau

10521 Background: Little is known about neurotoxic mechanisms associated with chemotherapy in children with ALL. Cerebrospinal fluid (CSF) biomarkers of brain injury may provide insight into this process. Methods: 235 patients (51% male; mean [SD] age diagnosed 6.8 [4.7] years) treated on a chemotherapy only protocol provided CSF samples following diagnosis and through consolidation. CSF was assayed for biomarkers of myelin degradation (myelin basic protein [MBP]), neuronal damage (nerve growth factor [NGF], total-Tau [T-Tau]) and astrogliosis (glial fibrillary acidic protein [GFAP]). Leukoencephalopathy was evaluated by brain MRI’s during therapy. At ≥5 years post-diagnosis, 138 (70%) of the 198 still eligible survivors (without relapse and unrelated neurologic injury) completed neurocognitive testing and brain diffusion tensor imaging of white matter integrity at age 13.6 [4.6] years. Log-binomial and general linear models were used to examine whether biomarker changes from baseline through consolidation were related to serum methotrexate exposure, acute leukoencephalopathy, and long-term brain outcomes. Results: NGF and T-Tau increased from baseline to consolidation ( P's < 0.001), while MBP and GFAP were elevated at baseline and remained so through consolidation. The number of intrathecal injections (methotrexate, hydrocortisone, cytarabine) was positively correlated with NGF increase at consolidation ( P= 0.005). Increases in GFAP (RR 1.2; 95% CI [1.0 – 1.4]), MBP (RR 1.1 [1.0 – 1.1]) and T-Tau (RR 1.8 [1.1 – 2.8]) were related to higher risk for acute leukoencephalopathy, and higher diffusivity in frontal lobe white matter at ≥5 years post-diagnosis ( P’s < 0.05). Increase in T-Tau at consolidation was associated with worse long-term sustained attention ( P= 0.03), and visual- ( P= 0.04) and visual-motor ( P= 0.02) processing speed. Conclusions: Glial injury, which is evident at diagnosis, may be related to leukemia and methotrexate exposure. Neuronal injury is associated with intrathecal chemotherapy and long-term neurocognitive and brain imaging outcomes. Monitoring CSF biomarkers may be useful in identifying individuals at risk for poor neurological outcomes.

scholarly journals Repeated Mild Traumatic Brain Injury Results in Long-Term White-Matter Disruption

2014 ◽  
Vol 34 (4) ◽  
pp. 715-723 ◽  
Author(s):  
Virginia Donovan ◽  
Claudia Kim ◽  
Ariana K Anugerah ◽  
Jacqueline S Coats ◽  
Udochuwku Oyoyo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Health Concern ◽  
Sprague Dawley ◽  
G Ratio

Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to the left cortex of rmTBI animals. Shams received only a craniectomy. Ex vivo diffusion tensor imaging (DTI), transmission electron microscopy (TEM), and histology were performed on the anterior corpus callosum at 60 days after injury. The rmTBI animals showed a significant bilateral increase in radial diffusivity (myelin), while only modest changes in axial diffusivity (axonal) were seen between the groups. Further, the rmTBI group showed an increased g-ratio and axon caliber in addition to myelin sheath abnormalities using TEM. Our DTI results indicate ongoing myelin changes, while the TEM data show continuing axonal changes at 60 days after rmTBI. These data suggest that bilateral rmTBI induced 7 days apart leads to progressive alterations in white matter that are not observed after a single mTBI.

scholarly journals Cordycepin confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Pengju Wei ◽  
Ke Wang ◽  
Chen Luo ◽  
Yichen Huang ◽  
Dilidaer Misilimu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Macrophage Polarization ◽  
Neutrophil Infiltration ◽  
Tissue Loss ◽  
Immunological Mechanism ◽  
Neutrophil Depletion ◽  
Neuroprotective Function

Abstract Background The secondary injury caused by traumatic brain injury (TBI), especially white matter injury (WMI), is highly sensitive to neuroinflammation, which further leads to unfavored long-term outcomes. Although the cross-talk between the three active events, immune cell infiltration, BBB breakdown, and proinflammatory microglial/macrophage polarization, plays a role in the vicious cycle, its mechanisms are not fully understood. It has been reported that cordycepin, an extract from Cordyceps militaris, can inhibit TBI-induced neuroinflammation although the long-term effects of cordycepin remain unknown. Here, we report our investigation of cordycepin’s long-term neuroprotective function and its underlying immunological mechanism. Methods TBI mice model was established with a controlled cortical impact (CCI) method. Cordycepin was intraperitoneally administered twice daily for a week. Neurological outcomes were assessed by behavioral tests, including grid walking test, cylinder test, wire hang test, and rotarod test. Immunofluorescence staining, transmission electron microscopy, and electrophysiology recording were employed to assess histological and functional lesions. Quantitative-PCR and flow cytometry were used to detect neuroinflammation. The tracers of Sulfo-NHS-biotin and Evans blue were assessed for the blood-brain barrier (BBB) leakage. Western blot and gelatin zymography were used to analyze protein activity or expression. Neutrophil depletion in vivo was performed via using Ly6G antibody intraperitoneal injection. Results Cordycepin administration ameliorated long-term neurological deficits and reduced neuronal tissue loss in TBI mice. Meanwhile, the long-term integrity of white matter was also preserved, which was revealed in multiple dimensions, such as morphology, histology, ultrastructure, and electrical conductivity. Cordycepin administration inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization after TBI. BBB breach was attenuated by cordycepin administration at 3 days after TBI. Cordycepin suppressed the activities of MMP-2 and MMP-9 and the neutrophil infiltration at 3 days after TBI. Moreover, neutrophil depletion provided a cordycepin-like effect, and cordycepin administration united with neutrophil depletion did not show a benefit of superposition. Conclusions The long-term neuroprotective function of cordycepin via suppressing neutrophil infiltration after TBI, thereby preserving BBB integrity and changing microglia/macrophage polarization. These findings provide significant clinical potentials to improve the quality of life for TBI patients.

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